Target-derived GFRα1 as an attractive guidance signal for developing sensory and sympathetic axons via activation of Cdk5
Target-derived GFRα1 as an attractive guidance signal for developing sensory and sympathetic axons via activation of Cdk5
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DOI：
10.1016/s0896-6273(02)01002-4
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发表时间：
2002-10-24
期刊：
影响因子：
16.2
通讯作者：
Ibáñez, CF
中科院分区：
文献类型：
--
作者：
Ledda, F;Paratcha, G;Ibáñez, CF
固定的和可扩散的分子线索调节发育过程中的轴突引导。GFRalpha1是一种GPI锚定的GDNF受体，在靶神经支配过程中，由副神经细胞和发育中的感觉神经元和交感神经元的外周靶点以膜结合和分泌的形式表达。GFRalpha1在轴突发育中的相对缺陷允许外源性GFRalpha1捕获GDNF并将其呈递给轴突c-Ret受体识别。外源性GFRalpha1促进轴突生长，在GDNF浓度均匀的情况下，通过为表达c-Ret的轴突创造位置信息，起到长程定向信号的作用。可溶性GFRalpha1可延长GDNF介导的细胞周期蛋白依赖性激酶5(CDK5)的激活，这是GFRalpha1诱导的轴突生长和轴突引导所必需的事件。靶向衍生的GFRalpha1与GDNF一起，可以非细胞自主的方式发挥作用，作为一种化学吸引信号，具有促进外周神经元生长的活性。
Immobilized and diffusible molecular cues regulate axon guidance during development. GFRalpha1, a GPI-anchored receptor for GDNF, is expressed as both membrane bound and secreted forms by accessory nerve cells and peripheral targets of developing sensory and sympathetic neurons during the period of target innervation. A relative deficit of GFRalpha1 in developing axons allows exogenous GFRalpha1 to capture GDNF and present it for recognition by axonal c-Ret receptors. Exogenous GFRalpha1 potentiates neurite outgrowth and acts as a long-range directional cue by creating positional information for c-Ret-expressing axons in the presence of a uniform concentration of GDNF. Soluble GFRalpha1 prolongs GDNF-mediated activation of cyclin-dependent kinase 5 (Cdk5), an event required for GFRalpha1-induced neurite outgrowth and axon guidance. Together with GDNF, target-derived GFRalpha1 can function in a non-cell-autonomous fashion as a chemoattractant cue with outgrowth promoting activity for peripheral neurons.